Disinfecting oral rinse compositions and process for using the same

ABSTRACT

This invention relates generally to compositions and methods useful for oral hygiene rinses, and more specifically to oral rinses in which the antimicrobial activity of chlorous acid is supplemented by that of lactic acid as one of a combination of antimicrobial acids, preferably acids which serve to partially convert chlorite ion to chlorous acid.

TECHNICAL FIELD

[0001] This invention relates generally to compositions and methodsuseful for oral hygiene rinses, and more specifically to oral rinses inwhich the antimicrobial activity of chlorous acid is supplemented bythat of lactic acid as one of a combination of antimicrobial acids,preferably organic acids, which serve to partially convert chlorite ionto chlorous acid.

BACKGROUND OF THE INVENTION

[0002] In the last few decades a large number of antimicrobial systemshave been developed that are based on the in-situ creation of metastablechlorous acid, under conditions where the chlorous acid, HClO₂,represents a relatively small fraction of the total aqueous chlorite(ClO₂ ⁻). The antimicrobially-effective chlorous acid systems functionat pH values from about 3.5 down to about 2.5. The protic acid source toeffect this conversion is generally an organic acid. These acidifiedchlorite compositions were first taught by Alliger in 1978 (U.S. Pat.No. 4,084,74) and in 1982 (U.S. Pat. No. 4,330,531), as germ-killingcompositions with a broad-range of high activity against bacteria, fungiand viruses. In Alliger's compositions the acid activator, lactic acid,was deemed to be critical, and the quantity of lactic acid utilized hadto represent at least about 15% by weight of the total amount of organicand inorganic acids present. Subsequently Tice, in 1986 (U.S. Pat. No.4,585,482), disclosed long-active biocidal compositions in which sodiumchlorite is slowly activated by the slow degradation of acid-generatingpolymers, such as poly(lactic acid). Several patents followed thereafterin which lactic acid, among other protic acids, was used in combinationwith chlorite salts for the purpose of skin disinfection, specificallyas components of barrier formulations (U.S. Pat. No. 4,891,216), agenital herpes treatment (U.S. Pat. No. 4,956,184), or inanti-inflammatory formulations (U.S. Pat. No. 5,384,134).

[0003] Subsequent prior art taught the creation of a diverse range ofchlorous acid compositions and their method of use. All but one (U.S.Pat. No. 5,820,822) were based on the use of protic acids, primarilyorganic acids, to transform chlorite to chlorous acid. These organicacids did not include lactic acid, as a result of Alliger's earlierdisclosure of lactic/chlorite disinfection systems, wherein lactic acidwas required to be at least 15% by weight of all acids present. Thesesubsequent art disclosures are embodied in U.S. Pat. No. 4,986,990(1991), U.S. Pat. No. 5,185,161 (1993) and RE36,064 (1999), all issuedto Davidson and Kross. A process for using chlorous acid solutions toremove bacteria from poultry and other meats, issued to Kross (U.S. Pat.No. 5,389,390), included lactic acid as a prospective acidifying agentfor the chlorite, but it was also disclosed that technical-grade lacticacid was inappropriate for such use because impurities in commercialsources of lactic acid caused the unwanted generation of chlorinedioxide (ClO₂), and this was found to cause undesirable discolorationand bleaching of poultry skin This inventor has also noted that ClO₂causes similar, undesirable staining of protein deposits in soft contactlenses, following repeated use of the lenses and their subsequentdisinfection in a ClO₂ solution. The discoloration is most probablyascribable to the oxidative transformation, by ClO₂, of labile aminoacids (specifically tyrosine and tryptophan) in common proteins, to formcolored materials (see Masschelein).

[0004] In the patent issued to Kross et al. (U.S. Pat. No. 5,100,652)“Disinfecting Oral Hygiene Compositions and Process for Using the Same,”which was based on chlorite solutions activated by an organic acid,lactic acid was specifically excluded from the list of organic acidsthat might be used in such solutions. Although this exclusion wasnecessary because of the earlier teachings of Alliger, lactic acid atthat point was deemed to be an inappropriate mouth rinse acidifier,owing to its particularly undesirable sour taste. Thus its exclusion wasnot considered as limiting, when formulating effective, commercializableantimicrobial oral formulations. In the practice of the technologydisclosed in Kross' oral hygiene U.S. Pat. No. 5,100,652, this sameinventor has since learned that formulations which contain glycerin,particularly at levels above about 10% in the mixed composition, resultin unacceptable staining of users' teeth. The use of such compounds,which contain vicinal hydroxy groups, were taught in that patent to be ameans of releasing chlorine dioxide into the oral rinse for additionalgermicidal benefit. Nevertheless the adverse discoloration of teeth isnow recognized to derive from chlorine dioxide, whether generated byglycerin-like compounds or the impurities associated withtechnical-grade lactic acid. At lower levels of ClO₂ in oral rinsecompositions the adverse staining effects take longer to notice, but forrinse products which are used twice-daily, for months and years, theincreasing discoloration would dissuade consumers from further use. Thusthe inappropriate taste of lactic acid as well as the propensity ofnormal, commercial lactic acid to cause unwanted tooth staining, wouldseem to argue strongly against its potential inclusion in oral rinseformulations.

[0005] Subsequent oral compositions based on acidified chlorite systemsare those taught by Lukacovic et al. (U.S. Pat. No. 5,281,412), in whichacidified chlorite solutions require a citrate ion source to reducestaining, and Witt et al. (U.S. Pat. Nos. 6,077,502 and 6,132,702) wherethe chlorite solutions are above pH 7, and contain effectively no ClO₂or chlorous acid.

[0006] Continued experiments intended to optimize the efficacy of oralrinse solutions has led this inventor to review and reconsider thepotential contribution of lactic acid to these systems. This need wasbased on the fact that chlorous acid oral rinse systems are short lived,and subject to loss of activity upon salivary dilution and the resultantpH rise, while many organic acids will maintain some level ofgerm-killing activity in solutions with H⁺ concentrations one-tenth orless of their initial level in the chlorous acid oral rinse. There-investigation of lactic acid specifically was driven by the fact thatlactic acid is the most effective antimicrobial acid among those listedby the US Food & Drug Administration as Generally Recognized As Safe(GRAS) as food acidulants. The GRAS designation is accorded to materialswhich possess the highest recognized safety for food use; and GRASacids, therefore, are the most appropriate to use forpotentially-ingestible oral hygiene compositions. It is well recognizedthat lactic acid is more effective, for example, than malic, citric,tartaric, succinic, adipic, and fumaric acids, which are all GRAS acids.Among these acids, other than lactic, malic acid is the most activegermicide, but when compared with lactic acid, it is significantly lesseffective. When lactic acid was compared with malic acid, on the basisof equimolar amounts of the unionized acid form, using an AOAC[Association of Official Analytical Chemists] Germicidal Test procedure,malic acid destroyed 1.45 logs₁₀/ml organisms of an initial inoculum ofE. coli of 7.63 logs₁₀/ml, whereas lactic acid killed 4.15 logs₁₀/ml ofthe same population. Numerically, after disinfection, there were ˜1500times more residual E. coli organisms, per ml of solution, in the malicacid-treated suspension as there were in the lactic-acid treatedsuspension.

[0007] As already indicated, the impediments to the use of lactic acidin an oral rinse are its unpleasant taste and its tendency to triggerundesirable ClO₂ formation in chlorite solutions, when included as thetechnical-grade material. The latter is generally ˜88% pure, and is theonly form available commercially in appropriate bulk quantity, at a costless that $1 per lb. This is in contrast to the limited quantities of“pure” (98%) lactic acid available from specialty chemical houses, at10-times that price.

[0008] This invention is the result of efforts to capitalize on thewell-recognized antimicrobial activity of lactic acid, as an auxiliarycidal agent to that of chlorous acid, while overcoming the limitationsimposed by lactic acid's unpleasant taste as well as the ClO₂-generatingimpurity effects of “technical-grade” lactic acid, the common commercialcommodity. I have discovered that there is a unique “window” between the“0”, proscribed use level for lactic acid as the sole organic acidactivator for chlorite in the Kross (U.S. Pat. No. 5,100,652)“Disinfecting Oral Hygiene Compositions.” disclosure, and Alliger'steaching that lactic acid must represent at least 15% by weight of theacid(s) required to activate chlorite in his disinfecting compositions.I have found that the high germicidal potency of lactic acid allows forits effective use at levels low enough to avoid unpleasant tastes, andparticularly, when included in the compositions in the manner taught inthe following disclosure, effectively overcomes the staining potentialengendered by ClO₂-triggering impurities in technical-grade lactic acid.The lactic acid use level, in combination with at least one otherorganic acid activator, satisfies all of the technical and organolepticrequirements listed above, while uniquely fitting into the 0 to <15%concentration range window stipulated in the prior art.

OBJECTS OF THE INVENTION

[0009] It is, therefore, an object of the present invention to provide acomposition and a process for the use of lactic acid to enhance andprolong the antimicrobial capabilities of acidified-chlorite oralhygiene formulations.

[0010] It is a further object of this invention to achieve a level ofuse of lactic acid in these oral rinses, in combination with at leastone other organic acid activator, such that the resulting taste of theoral composition is not adversely impacted by the unpleasant flavor oflactic acid.

[0011] It is yet a further object of this invention to include lacticacid in the acid-activator component of acidified-chlorite oral rinsesin a manner so as to minimize the formation of chlorine dioxide, andthereby avoid undesirable teeth staining.

[0012] And it is yet a further object of this invention to achieve theprevious objects by employing lactic acid in these acid-chlorite rinsesat levels which have not been previously taught.

[0013] These, and/or other objects of the present invention may bereadily gleaned from a detailed review of the description of theinvention which follows:

SUMMARY OF THE INVENTION

[0014] The present invention relates to the discovery that low levels oflactic acid in two-part acid-chlorite oral hygiene compositions,specifically between about 2% of the total weight of the acid activatorsand less than about 12% by weight of the acid activators of the chloritefound in the final composition, can enhance the germicidal qualities ofsuch compositions. Specifically this range of levels circumvents theadverse negative taste that would be imparted to acid-chlorite oralcompositions were lactic acid to be used either alone as the acidactivator, or at levels greater than about 15% by weight of combinedacids present. The antimicrobial benefit of the lactic acid, even atthese prescribed use levels, results from its significantly greatergermicidal efficacy than that of any other available acid, suchavailability being based on the acknowledged safety of such acids inorally-ingested products, as well as the palatability of the acid.

[0015] It has been further discovered that the adverse tooth stainingqualities engendered by the use of commonly-available lactic acid insuch oral rinse compositions, based on the impurities in thetechnical-grade product, can be overcome through the in-situ creation oflactic acid in the acid-part from its corresponding metal salt(preferably, water soluble and more preferably the sodium or potassiumsalt of lactate), by appropriate addition to that part of an equivalentamount of a stronger acid (i.e., having a pK_(a) which is lower thanthat of lactic acid at 3.86), either inorganic (e.g., mineral acid) ororganic, or a weaker acid which has been included in sufficient excessto the lactic acid to create the lactic acid. The amount of metallactate salt selected for use is such that the level of lactic acidcreated therefrom is in the above-specified 2% to 12% (i.e., about 2% toabout 12% by weight of the acids used in the composition) relativeweight range.

[0016] In one aspect of this invention, the lactate salt is calciumlactate which, upon acidification to liberate free lactic acid, providescalcium ions to the composition, of benefit in suppressingdemineralization of tooth enamel. In another aspect the lactate salt issodium lactate, which use is favored when fluoride ion is included inthe composition.

[0017] The pH of the oral rinse system comprised of lactic acid and atleast one other acid, and a metal chlorite salt, will generally lie inthe range of about 2.5 and about 3.5, the specific value thereof beingdependent upon the nature and quantity of the acids present and, to alesser extent, the quantity of metal chlorite salt used in the mixedcomposition. The amount of metal chlorite in the composition rangespreferably from about 0.05% to about 0.5% based on the total weight ofthe composition. Other agents may be used in these compositions toimpart such other desired qualities as color (coloring agents), flavor(flavoring agents), aroma (aromatic agents), texture (texturizingagents), surfactancy (surfactants, emulsifiers), and suppressed toothdemineralization. These well-known components may be added in effectiveamounts to compounds according to the present invention.

[0018] Methods of using compositions according to the present inventionin oral hygiene formulations to reduce microbial growth in the mouth amammal are other aspects of the present invention. In this method, acomposition according to the present invention is used as an oralhygiene rinse in the mouth of a mammal, preferably a human, for a periodsufficient (generally, at least about 5-10 seconds and upwards ofseveral minutes or more) to reduce microbial growth in the mouth of themammal.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

[0019] The term “chlorite” or “chlorite salt” is used throughout thespecification to describe a salt of chlorite which is readily soluble inan aqueous system and which readily dissociates into chlorite anion andcounterion (generally, metal). Two particularly preferred salts ofchlorites for use in the present invention include sodium chlorite andpotassium chlorite.

[0020] The term “acid” or “acid activator” is used throughout thespecification to describe protic acids, i.e., acids that releasehydrogen ions in solution, which may be combined with lactic acid toproduce compositions according to the present invention. Acids for usein the present invention may include inorganic acids such ashydrochloric, sulfuric and nitric acid, benzenesulfonic acid, amongother organic sulfonic acids, but preferably, include organic acids suchas acetic, benzoic, citric, fumaric, glycolic, malic, maleic, tartaricacid, citric, propionic, acetic, succinic, adipic, and mandelic, amongothers, including ethylenediaminetetraacetic acid (EDTA, as the freeacid or the monosodium salt), among numerous others. It is noted thatnumerous additional acids may also be used in the present invention. Inits broadest aspect, compositions according to the present invention maymake use of virtually any orally compatible acid in combination withlactic acid, to the extent that it provides an initial pH, which whenthe chlorite-containing part and the acid-containing part are combinedto produce an initial pH preferably ranging from about 2.5 and about3.5. One of ordinary skill will be able to readily determine the typeand amount of acid to be used for a particular application.

[0021] The term “effective” is used to describe concentrations ofamounts of individual components according to the present inventionwhich are included in compositions in order to produce an intendedeffect. In the case of the use of the term “effective” with respect tothe time of an application, such definition is that amount of time whichis used to produce an intended result, for example, the decrease innumbers or growth of microbial flora within the mouth.

[0022] The oral hygiene rinse compositions of this invention compriseaqueous solutions containing a suitable amount of two or more carboxylicacids, one acid of which is lactic acid such that its total amount isnot greater than about 12% of the total weight of such acids, a suitableamount of a metal chlorite at a pH adjusted to favor its stability, andone or more flavoring agents. The compositions are prepared for usedirectly prior to oral intake, generally by combination of equal volumesof two aqueous parts. One part is comprised of the acids and flavor; theother part is comprised of the metal chlorite. Typically the amount ofcombined acids is sufficient to reduce the pH of the mixed oral rinse tobetween about 3.5 and about 2.5. The amount of metal chlorite in themixed oral rinse is typically in the range of about 0.05% to about 0.5%.

[0023] In a preferred embodiment the lactic acid is prepared in situ bystoichiometric combination of a lactate salt and a strong inorganic acidother than phosphoric acid, or by combination of a lactate salt andanother carboxylic acid of an acid strength greater than that of lacticacid, such that the calculated degree of conversion of the lactate tolactic acid is at least 70% (i.e. the calculated molar ratio of lacticacid to lactate ion is at least 2.3). In certain embodiments of thisinvention the carboxylic acids that are used in combination with thelactic acid are those accorded the GRAS status by the FDA, so that thepartial ingestion of the oral hygiene rinse during use, which occurs toabout the 10% level, will cause no untoward toxicological effects. Thelist of GRAS carboxylic acids, besides lactic acid, includes malic,citric, tartaric, succinic, adipic, and fumaric acids. Benzoic acid isalso a GRAS acid, and its presence in the inventive composition willalso supplement the antimicrobial qualities of the acid-chloritecomposition Among these embodiments, malic acid is a preferred acidifierfor the chlorite salt, since its immediate perceived taste sensation isless than most of the other carboxylic acids, such as citric, whichpromotes a very rapid sour burst in the mouth. Another embodimentincludes the non-GRAS acid, mandelic acid, which has significantgermicidal properties, but an oral rinse formulation containing thisacid would require significant toxicological testing to validate itssafety.

[0024] The level of about 12% lactic acid by weight of total carboxylicacid in the composition, represents an apparent threshold, above whichthe flavor of lactic acid per se becomes perceptible as compared withthat of a composition prepared without it, using the same othercarboxylic acid. This is a variable figure, depending to a significantdegree on the sensitivity of the user and the flavor characteristics ofthe other acid. When citric acid is used as the supplemental acid, lesstotal acid is required to achieve a desired pH than, say, when usingmalic acid, which is half the strength of citric (K_(a1) of citric is8.2×10⁻⁴ vs. 3.9×10⁻⁴ for malic acid). Thus a smaller amount of lacticacid is used when it represents, say, 10% of a lactic/citric combinationthan a lactic/malic combination; but the tart taste of citric, reducedby its relatively lower level, can be similarly intruded upon by that ofthe lactic. Thus it is important, in practicing this invention, toconduct taste-evaluations of candidate carboxylic acids other thanlactic acid alone, to determine the proper level for a desired pH, priorto supplementation with lactic acid to levels from about 2% to about 12%of the total weight of the combined acids.

[0025] In certain embodiments, the metal lactate in these compositionsis an alkali, an alkaline earth lactate, or a heavier metal lactate. Thealkali metal lactate class includes the lactic acid salts of sodium,potassium and ammonium, of which sodium lactate is the preferred sourceof regenerated acid. Useful alkaline earth metal lactates includemagnesium and calcium lactate. Available heavier metal lactates areferrous and aluminum lactates, although the cation flavor is intrusive.The amount of metal lactate salt selected for use is such that the levelof lactic acid created therefrom is in the above-specified 2% to 12%relative weight range. It has been found generally that at the strongerend of the inventive pH range, between about 2.5 and about 3.0, thelevel of metal lactate required for suitable germicidal efficacy is atthe lower end of the inventive range, i.e. from about 0.05% to about0.25% in the mixed composition. At pH values between about 3.0 and about3.5, metal lactate levels between about 0.25% and about 0.5% are neededfor comparable efficacy of the chlorous acid system. Factoring intothese considerations is the fact that the germicidal enhancementprovided by the lactic acid depends on the relative amount of the freeacid form (the active cidal species) with respect to that of the lactateion. At pH 2.5 96% of the two lactic species exist as lactic acid, whichdrops to 70% at pH 3.5. At higher pH values, the reduced amount of theintact lactic acid molecule (e.g. 42% of total, at pH 4.0) no longerwarrants its inclusion as a germicidal enhancer.

[0026] The lactic acid can be included in the acid activator portion,from about the 2% to about the 12% level with respect to the weight ofthe multiple acids in the activator, using either the intact acid or asa lactate salt which is converted, during preparation, to the whole acidform. The intact acid is currently available, on an economic basis, asthe technical grade liquid material with a degree of purityapproximating 88%. When that material is employed, it is necessary todetermine its percent purity by such standard procedures as theback-titration method provided in the United States Pharmacopeia. Whenusing the metal lactate salt, the desired weight of final acid must bedetermined by calculation, so as to lie within the stipulated 2% toabout 12% range as percentage of total activating acids. For example, toachieve a specific percentage level of lactic acid with respect to thetotal weight of the activating acids, it is necessary to first determinethe actual weight of lactic acid that is desired to be in the acidcomposition, and then multiply by the relative molecular weights of themetal salt and lactic acid. For sodium lactate, the multiplicationfactor would be 112.07÷90.08, or 1.244. For a multivalent lactate salt,its molecular weight should be divided the metal's valence. Correctionsfor lactate impurities should also be made, as for example dividing thecalculated weight of sodium lactate by the fractional concentration inthe commercially-available solution form, usually of 70%-80% purity.

[0027] Other materials may be incorporated into either of the two partsof the inventive compositions, so as to improve the stability of eachpart, as well as improve and/or enhance the organoleptic qualities, thesafety, and the efficacy of the mixed acidified chlorite composition.The stability of the aqueous chlorite phase is generally favored by pHvalues over about 8.5, preferably over 9.2, and most preferably over10.0. Adjustment of pH can be accomplished by use of standard alkalinematerials known to those skilled in the art, such as sodium or potassiumhydroxide. Additional components which have value in certain embodimentsinclude surface active agents, colorants, humectants, flavorants,sweeteners, fluoride ion sources, calcium sources and thickeners.Appropriate members of these classes are known to experienced oral rinseformulators, and need not be specifically identified herein. Levels ofuse of these materials are typically the following, expressed on themixed formulation basis: Surface active agents (about 0.05% to about5.0%), humectants (from about 0% to about 25%, with care taken that thelevel of humectant selected causes no undue triggering of chlorinedioxide formation from acidified chlorite), flavoring agents (from about0.04% to about 2.0%), sweeteners (artificial and natural) (from about0.02% to about 3.0%), and coloring agents (from about 0.0001% to about0.2%).

[0028] Preferred compositions include fluoride ion, to suppress enameldemineralization and caries formation in teeth. Typical fluoride ionlevels are from about 0.02% to about 0.30% of the final composition,derived from fluoride sources such as sodium fluoride, stannousfluoride, indium fluoride and sodium monofluorophosphate. Thickenershave the advantage of extending the presence of the rinse in the oralcavity, by virtue of the attendant resistance to salivary dilution. Theyare typically used at levels from about 0% to about 5% in theseinventive compositions. In a preferred composition xanthan gum has beenfound to offer the advantage of stability in both the acid activator andthe chlorite phases. Generally the colorants and flavorants are selectedto be both aesthetically appealing and of sufficient stability, in boththe part in which they are included and in the mixed composition, whichis an oxidizing environment.

[0029] The following non-limiting examples further describe preferredembodiments within the scope of the present invention. Many variationsof these examples are possible without departing from the spirit of theinvention.

EXAMPLE 1

[0030] This examples demonstrates the tendency for lactic acid,technical grade, to cause unwanted amounts of chlorine dioxide in anoral rinse solution, as compared with an equivalent-strength malic acidactivating solution, when combined with identical chlorite solutions.Based on the relative acid ionization constants for lactic and malicacids, i.e. 1.38×10⁻⁴ and 3.9×10⁻⁴, resp., equal volumes of 2.39%technical-grade (88%) lactic acid and 0.75% malic acid (pure) werecombined 1:1 with 0.32% (pure basis) sodium chlorite solutions that hadbeen adjusted to a pH ˜10.5. The acid and chlorite solutions had firstbeen equilibrated at 37° C., to simulate body temperature. The solutionpHs, in both cases, were 3.0. After 10 minutes, the solution Absorbancevalues were measured at a wavelength of 360 nM in a spectrophotometer,and the concentration of chlorine dioxide (ClO₂) then calculated, usingthe molar extinction coefficient of 1,242 liter/mole.cm. A concentrationof 7.1 ppm of ClO₂ was found in the lactic acid/chlorite oral rinsesolution, and <1 ppm ClO₂ in the malic acid/chlorite rinse solution.

[0031] The rapid generation of ClO₂, with its tooth-staining potential,particularly after repeated daily use, clearly minimizes the value oforal rinse solutions containing the significant levels of ClO₂associated with the use of technical-grade lactic acid as the solechlorite activator.

EXAMPLE 2

[0032] This example shows the protein-staining caused by the ClO₂generated in the lactic/chlorite solution prepared in Example 1, ascompared with that from the malic/chlorite oral rinse. 1 ml offreshly-isolated liquid egg albumen was added to 5 ml of each of the tworinse solutions and a malic/water control. The albumen protein in thelactic/chlorite solution turned pink immediately, while there was nodiscoloration noted in either the malic acid solution or the control.This demonstrates how ClO₂, as triggered by the lactic acid impurities,will cause demonstrable staining of the proteins commonly found on toothsurfaces, particularly the pellicle and bacterial plaque.

EXAMPLE 3

[0033] This example demonstrates how technical-grade lactic acid may beused in combination with another organic acid, as a mixed activator of achlorite solution, so that no perceptible increase of ClO₂ is found tooccur in the solution, as compared with a one-part acid activator withthe other, non-lactic acid. A mixture was prepared with 0.75% malic acidand 0.116% technical-grade lactic acid, containing 0.102% pure lacticacid, wherein lactic acid represented 12.0% by weight of the total acidsin the activator. An activator containing malic acid alone was prepared,containing 0.786% malic acid [0.75%+0.036%; i.e. the malic equivalent ofthe 0.116% lactic acid]. These solutions, after equilibration at 37° C.,were mixed in equal volumes with similarly-equilibrated solutionscontaining 0.32% sodium chlorite, on a pure basis, having a pH of 10.5.Upon mixture, both oral rinses had pHs of 2.96. Spectrophotometricanalysis of the two solutions, as in Example 1, indicated that less than1 ppm of ClO₂ was generated after 10 minutes. When 1 ml of fresh albumenwas added to 5 ml aliquots of each of the two oral rinse solutions, asin Example 2, no pink color developed in either tube, indicating aminimum tendency to discolor protein.

EXAMPLE 4

[0034] This example demonstrates that lactic acid can be prepared from alactate metal salt, and used in combination with a metal chloritesolution, as in Example 1, without creation of significant quantities ofClO₂. A portion of calcium lactate was dried in a 105° C. oven, and asufficient quantity of the desiccated powder was added to water to makea 2.54% aqueous solution. Prior to final dilution, a stoichiometricamount of hydrochloric acid (4.7 ml of 5.0N) was added to the solutionto convert the calcium lactate to free lactic acid, to the degree thatobtains at the pH of the acid solution. Upon combination of thatsolution, equilibrated to 37° C., with an equal volume of a 0.32% sodiumchlorite solution, at pH 10.5 and at 37° C., the solution was allowed tostand 10 minutes and its Absorbance at 360 nM was measuredspectrophotometrically. The reading corresponded to a ClO₂ level of <1ppm, as compared with the 7.1 ppm found in Example 1 when a comparableamount of technical-grade, free lactic acid was utilized. Addition of 1ml of fresh egg albumen to 5 ml of the lactate-derived oral rinseresulted in no discoloration of the protein, which confirms that theabsence of significant ClO₂ levels minimizes the potential stainingproblem.

[0035] However, the taste of the lactate-derived oral rinse was highlyobjectionable, and corresponded to the sour, off-taste of the lacticacid rinse of Example 1. Thus the use of lactic acid as the single acidactivator of a metal chlorite, to serve as an acceptable oral hygienerinse, is not at all feasible.

EXAMPLE 5

[0036] This example is a counterpart of Example 3, with the exceptionthat the 12.0% lactic acid by weight of the mixed acid was hereincreated by acidification of calcium lactate, thereby avoiding theintroduction of ClO₂-generating lactic acid impurities. Specifically,0.1235 gms of anhydrous calcium lactate was added to 0.75 gms of malicacid (pure), which was dissolved in sufficient water to bring the totalvolume to 100 ml after the addition of 1.13 ml of 1N hydrochloric acid.The latter was sufficient to convert the lactate ion to lactic acid, tothe degree that occurs at the pH of the acid mix. This solution, afterequilibration at 37° C., was mixed with an equal volume of asimilarly-equilibrated solution containing 0.32% of sodium chlorite, ona pure basis, having a pH of 10.5. Upon mixture, the oral rinse had a pHof 2.98. The taste of the product was acceptable as an oral rinse, eventhough it had no excipients to improve its organoleptic qualities, e.g.flavor, sweetener, color.

EXAMPLE 6

[0037] This example provides a more-acceptable, commercializable oralhygiene product that contains appropriate excipients for both aestheticappeal and improved functionality, as compared with a corresponding oralrinse lacking the specified ingredients. The acid activator solution ofExample 5 is prepared by first addition of 0.05% sodium benzoate to thebulk of the water, followed by 0.05% sodium saccharin, and 0.20% ofxanthan gum with subsequent mixing. After dispersal of the latter, thecalcium lactate and malic acid are added, in the amounts specified,followed by 0.0002% of FD&C Blue #1. After the gum has fully hydrated,an amount of 1N hydrochloric acid is then carefully and slowly added toreduce the solution pH to 2.8-2.9. The water volume is brought to ˜95%of the required volume, and then an amount of L-menthol crystals aredissolved in the mixture with continuous stirring. Upon completedissolution, the volume is increased to the final desired value.

[0038] The chlorite phase of the oral hygiene product is prepared from afresh dispersion of 0.2% xanthan gum, to which is added an amount ofsodium chlorite, based on its degree of purity, sufficient to form a0.32% aqueous solution. To that solution is added enough sodium fluorideto make a 0.08% solution, and a quantity of alkali needed to bring thesolution pH to the pH 10.5-10.8 range.

[0039] The admixture of equal volumes of the acid activator solution andthe chlorite solution provides an antimicrobial oral rinse that isorganoleptically acceptable, causes no tooth staining, and combinesimmediate germicidal activity from the chlorous acid system with theextended antimicrobial action provided by lactic acid. The slightthickening of the formula, with xanthan gum, is of benefit to bothgermicidal components, since it suppresses the dilution of the rinse bysaliva, and thereby prolongs the life of the chlorous acid system andthe level of lactic acid with respect to its lactate ion counterpart.References Cited U.S. Patent Documents Number Issue Date Inventor U.S.Class 4084747 April, 1978 Alliger 239/4 4330531 May, 1982 Alliger424/149 4585482 April, 1986 Tice et al. 106/15 4891216 Jan., 1990 Krosset al. 424/78 4986990 Jan., 1991 Davidson et al. 424/665 5100652 May,1992 Kross et al. 424/53 5185161 Feb., 1993 Davidson et al. 424/6655384134 Jan., 1995 Kross et al. 424/661 5389390 Feb. 1995 Kross 426/3325597561 Jan., 1997 Kross 424/78 5628959 May, 1997 Kross 422/37 5651977July, 1997 Kross 424/419 5772985 June, 1998 Kemp et al. 424/45 5820822Oct., 1998 Kross 422/37 RE36,064 Jan., 1999 Davidson et al. 424/6656063425 May, 2000 Kross 426/335 6077502 June, 2000 Witt et al. 424/536096350 Aug., 2000 Kemp et al. 424/661 6132702 Oct., 2000 Witt et al.424/53

[0040] Other References

[0041] Masschelein, W J; (1979) Chlorine Dioxide; Chemistry andEnvironmental Impact of Oxychlorine Compounds. Ann Arbor Science, Mich.

I claim:
 1. An antimicrobial oral hygiene rinse composition comprisingwater and an effective amount of a chlorite salt in combination with anacid combination comprising lactic acid and at least one additionalacid, said acid combination producing in combination with said chloritesalt a pH ranging from about 2.5 to about 3.5, said lactic acidcomprising about 2% to about 12% by weight of said acid combination. 2.The composition according to claim 1 wherein said additional acid isselected from the group consisting of hydrochloric, sulfuric, nitricacid, organic sulfonic, acetic, benzoic, citric, fumaric, glycolic,malic, maleic, tartaric acid, citric, propionic, succinic, adipic,mandelic, ethylenediaminetetraacetic acid, and ethylenediaminetetraceticacid monosodium salt.
 3. The composition according to claim 1 whereinsaid chlorite salt ranges from about 0.05% to about 0.5% by weight ofsaid composition.
 4. The composition according to claim 1 wherein saidchlorite salt is sodium chlorite or potassium chlorite.
 5. Thecomposition according to claim 1 wherein said lactic acid is prepared insitu by the stoichiometric combination of a lactate salt and an acidhaving a pK_(a) of less than lactic acid and/or an excess of an acidwhich has a pK_(a) which is greater than lactic acid.
 6. The compositionaccording to claim 1 wherein said composition further comprises at leastone additive agent selected from the group consisting of surface activeagents, colorants, humectants, flavorants, sweeteners, fluoride ionsources, calcium sources and thickeners.
 7. A method of reducing thenumber of microorganisms in the mouth cavity of a mammal, said methodcomprising exposing said mouth cavity to a composition according toclaim 1 for a period of time effective to reduce the number ofmicroorganisms in said mouth cavity.
 8. A method of reducing the numberof microorganisms in the mouth cavity of a mammal, said methodcomprising exposing said mouth cavity to a composition according toclaim 2 for a period of time effective to reduce the number ofmicroorganisms in said mouth cavity.
 9. A method of reducing the numberof microorganisms in the mouth cavity of a mammal, said methodcomprising exposing said mouth cavity to a composition according toclaim 3 for a period of time effective to reduce the number ofmicroorganisms in said mouth cavity.
 10. A method of reducing the numberof microorganisms in the mouth cavity of a mammal, said methodcomprising exposing said mouth cavity to a composition according toclaim 4 for a period of time effective to reduce the number ofmicroorganisms in said mouth cavity.
 11. A method of reducing the numberof microorganisms in the mouth cavity of a mammal, said methodcomprising exposing said mouth cavity to a composition according toclaim 5 for a period of time effective to reduce the number ofmicroorganisms in said mouth cavity.
 12. A method of reducing the numberof microorganisms in the mouth cavity of a mammal, said methodcomprising exposing said mouth cavity to a composition according toclaim 6 for a period of time effective to reduce the number ofmicroorganisms in said mouth cavity.
 13. A method of reducing the numberof microorganisms in the mouth cavity of a mammal, said methodcomprising exposing said mouth cavity to a composition according toclaim 7 for a period of time effective to reduce the number ofmicroorganisms in said mouth cavity.